The goals of this proposed SCOR program are: 1) to generate new knowledge relating to the physiology, pathology, pharmacology, and epidemiolmgy chronic diseases of airways; and 2) to apply this knowledge of to the study of new modalities of therapy and prevention. We seek the effective integration of laboratory and clinical research and its focus on airways disease. Project 1 examines one important reservoir from which clinically significant disease arises, and seeks to explore the progression and reversibility of airways disease. Projects 3, 4, and 5 grapple with major issues of etiology: genetic, physiologic, pharmacologic, and environmental interactions which may provide and accelerate the pathophysiological changes leading to debilitating airways disease. Project 6 examines one of the consequences of airways dysfunction which leads to disability and respiratory failure. With Project 7 we begin to consider interventions; other aspects of disability and approaches to therapy are explored in Projects 8 and 9. The core units (Projects 10 and 11) provide essential services for the described research. We believe these projects represent a significant interdisciplinary attack directed toward chronic diseases of airways.